Tebas Pablo, Yang ShuPing, Boyer Jean D, Reuschel Emma L, Patel Ami, Christensen-Quick Aaron, Andrade Viviane M, Morrow Matthew P, Kraynyak Kimberly, Agnes Joseph, Purwar Mansi, Sylvester Albert, Pawlicki Jan, Gillespie Elisabeth, Maricic Igor, Zaidi Faraz I, Kim Kevin Y, Dia Yaya, Frase Drew, Pezzoli Patrick, Schultheis Katherine, Smith Trevor R F, Ramos Stephanie J, McMullan Trevor, Buttigieg Karen, Carroll Miles W, Ervin John, Diehl Malissa C, Blackwood Elliott, Mammen Mammen P, Lee Jessica, Dallas Michael J, Brown Ami Shah, Shea Jacqueline E, Kim J Joseph, Weiner David B, Broderick Kate E, Humeau Laurent M
Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
EClinicalMedicine. 2021 Jan;31:100689. doi: 10.1016/j.eclinm.2020.100689. Epub 2020 Dec 24.
A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described.
INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410.
The median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 10 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8 T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4.
INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses.
Coalition for Epidemic Preparedness Innovations (CEPI).
研发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗迫在眉睫。本文描述了一种针对SARS-CoV-2全长刺突抗原的DNA疫苗（INO-4800）所诱导的安全性和免疫原性。
INO-4800在两组各20名参与者中进行评估，分别皮内注射1.0毫克或2.0毫克疫苗，随后在第0周和第4周使用CELLECTRA® EP。39名受试者完成了两剂接种；2.0毫克组中有一名受试者在接受第二剂之前退出了试验。ClinicalTrials.gov标识符：NCT04336410。
中位年龄为34.5岁，55%（22/40）为男性，82.5%（33/40）为白人。到第8周，仅在5名受试者中观察到6例相关的1级不良事件。这些事件在第二次给药后频率均未增加。未报告严重不良事件。所有38名可评估免疫原性的受试者在接种第二剂INO-4800后均产生了细胞和/或体液免疫反应。到第6周，基于结合（酶联免疫吸附测定）和/或中和抗体（微量中和试验半数抑制浓度）反应，95%（36/38）的参与者血清转化，1.0毫克组和2.0毫克组中反应者结合抗体几何平均滴度分别为655.5 [95%置信区间（255.6，1681.0）]和994.2 [95%置信区间（395.3，2500.3）]。对于中和抗体，相应组中分别有78%（14/18）和84%（16/19）产生反应，几何平均滴度分别为102.3 [95%置信区间（37.4，280.3）]和63.5 [95%置信区间（39.6，101.8）]。到第8周，通过干扰素-γ酶联免疫斑点试验，1.0毫克组和2.0毫克组中分别有74%（14/19）和100%（19/19）的受试者产生T细胞反应，每10个外周血单核细胞的中位斑点形成单位分别为46 [95%置信区间（21.1，142.2）]和71 [95%置信区间（32.2，194.4）]。流式细胞术显示T细胞反应，以共同产生干扰素-γ和肿瘤坏死因子-α的CD8 T细胞为主，白细胞介素-4未增加。
INO-4800表现出优异的安全性和耐受性，并且通过引发体液或细胞免疫反应中的一种或两种，在100%（38/38）的接种受试者中具有免疫原性。
流行病防范创新联盟（CEPI）。
Zotero 插件
